Structural highlights
Function
3SPM_DENJA Inhibits ADP-induced platelet aggregation and inhibits the binding of purified platelet fibrinogen receptor alpha-IIb/beta-3 (ITGA2B/ITGB3) to immobilized fibrinogen (PubMed:1591238). Has also been described to inhibit cell adhesion to fibrinogen, fibronectin, laminin and collagen (PubMed:11336631, PubMed:16798616).[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Dendroaspin is a short chain neurotoxin homologue from the venom of Elapidae snakes, which lacks neurotoxicity. Unlike neurotoxins, it contains an Arg-Gly-Asp-(RGD)-motif and functions as an inhibitor of platelet aggregation and platelet adhesion with comparable potency to the disintegrins from the venoms of Viperidae. We have determined the structure of dendroaspin in solution using NMR spectroscopy. The structure contains a core similar to that of short chain neurotoxins, but with a novel arrangement of loops and a solvent-exposed RGD-motif. Dendroaspin is thus an integrin antagonist with a well defined fold different from that of the disintegrins, based on the neurotoxin scaffold.
Three-dimensional structure of the RGD-containing neurotoxin homologue dendroaspin.,Sutcliffe MJ, Jaseja M, Hyde EI, Lu X, Williams JA Nat Struct Biol. 1994 Nov;1(11):802-7. PMID:7634091[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wattam B, Shang D, Rahman S, Egglezou S, Scully M, Kakkar V, Lu X. Arg-Tyr-Asp (RYD) and Arg-Cys-Asp (RCD) motifs in dendroaspin promote selective inhibition of beta1 and beta3 integrins. Biochem J. 2001 May 15;356(Pt 1):11-7. PMID:11336631 doi:10.1042/0264-6021:3560011
- ↑ McDowell RS, Dennis MS, Louie A, Shuster M, Mulkerrin MG, Lazarus RA. Mambin, a potent glycoprotein IIb-IIIa antagonist and platelet aggregation inhibitor structurally related to the short neurotoxins. Biochemistry. 1992 May 26;31(20):4766-72. PMID:1591238 doi:10.1021/bi00135a004
- ↑ Lu X, Davies J, Lu D, Xia M, Wattam B, Shang D, Sun Y, Scully M, Kakkar V. The effect of the single substitution of arginine within the RGD tripeptide motif of a modified neurotoxin dendroaspin on its activity of platelet aggregation and cell adhesion. Cell Commun Adhes. 2006 May-Jun;13(3):171-83. PMID:16798616 doi:10.1080/15419060600726183
- ↑ Sutcliffe MJ, Jaseja M, Hyde EI, Lu X, Williams JA. Three-dimensional structure of the RGD-containing neurotoxin homologue dendroaspin. Nat Struct Biol. 1994 Nov;1(11):802-7. PMID:7634091
